👤 Zhongqiang Guo

To assess the association between the single nucleotide polymorphisms (SNP) rs174575 and rs2845574 of the fatty acid desaturase 2 (FADS2) gene and gestational diabetes mellitus (GDM). A total of 1 514 pregnant women who visited West China Second University Hospital of Sichuan University between January 1, 2013 and December 31, 2021 were enrolled in this study. Among them, 583 were diagnosed with gestational diabetes mellitus (GDM group), and 931 had normal pregnancies (control group). The SNPs rs174575 and rs2845574 of the FADS2 gene were analyzed using Sanger DNA sequencing. Plasma levels of insulin (INS), apolipoprotein A1 (apoA1) and apolipoprotein B (apoB) were measured using enzymatic methods, chemiluminescence and immunoturbidimetry. This study was approved by the Medical Ethics Committee of the West China Second University Hospital of Sichuan University (Ethics No.: 2020-036). The main genotype at the rs174575 C/G and rs2845574 C/T loci were CC in both GDM and control groups. No significant difference was found between the GDM and control groups regarding the genotypic or allelic frequencies of rs174575 and rs2845574 sites (P > 0.05). Among the GDM group, individuals with the GG genotype at the rs174575 site had lower plasma HDL-C levels compared to those with the CC genotype (P < 0.05), and had higher atherogenic indices (AI) compared with the CC and CG genotype (P < 0.05; P < 0.05). Individuals with the TT genotype at the rs2845574 site had higher AI compared with the CT genotype (P < 0.05). Among the control group, individuals with the GG genotype had lower diastolic blood pressure (DBP) compared to those with the CC genotype (P < 0.05). Additional subgroup analysis demonstrated that the rs174575 polymorphism was associated with AI levels in obesity subgroup of GDM, TG levels in non-obese subgroup of control and DBP levels in the obese subgroup of control (P < 0.05; P < 0.05; P < 0.05). The FADS2 rs174575 and rs2845574 polymorphisms in GDM patients are associated wit HDL-C and AI levels, and the FADS2 rs174575 polymorphisms was also associated with DBP levels in normal pregnant women. The AI and DBP levels have a BMI-dependent effect. Show less

This study aimed to investigate the role of Apolipoprotein B (Apo B) in diabetic nephropathy (DN) from epidemiological and genetic perspectives. We employed weighted multivariable-adjusted logistic regression to assess the relationship between ApoB and DN risk, utilizing data from the National Health and Nutrition Examination Survey spanning 2007-2016. Then, we used restricted cubic splines (RCS) to flexibly model and visualize the relation of predicted ApoB levels with DN risk. Subsequently, a bidirectional two-sample Mendelian randomization study using genome-wide association study summary statistics was performed. The primary Inverse Variance Weighted method, along with supplementary MR approaches, was employed to verify the causal link between ApoB and DN. Sensitivity analyses were conducted to confirm the robustness of the results. Our observational study enrolled 2242 participants with diabetes mellitus from NHANES. The multivariable logistic regression model indicated that elevated ApoB levels (>1.2 g/L), compared to low levels (<0.8 g/L), were significantly associated with DN risk (P < 0.05). The RCS model revealed a positive linear association with the risk of DN when ApoB levels exceeded 1.12 g/L (OR = 1.29, 95% CI: 1.07-1.57, P = 0.008). However, the MR IVW method did not reveal a direct causal effect of DN on ApoB (OR: 0.976; 95% CI: 0.950-1.004; P = 0.095), nor a direct causal effect of ApoB on DN (OR: 0.837; 95% CI: 0.950-1.078; P = 0.428). The evidence from observational studies indicates a positive correlation between ApoB levels exceeding 1.12 g/L and the onset of DN. However, the causal effects of ApoB on DN and vice versa were not supported by the MR analysis. Show less

Hepatic VLDL overproduction, tightly modulated by insulin signaling, plays a pivotal role in the progression of atherosclerosis (AS). The present study aimed to investigate whether inhibition of hepatic VLDL overproduction is a novel therapeutic strategy for the homogeneous tea polysaccharide (TPS3A) to ameliorate AS under insulin resistance (IR) conditions and the potential molecular basis involved. Results showed that TPS3A supplementation effectively alleviated systemic IR and delayed atherosclerotic plaque progression in HFD-exposed ApoE Show less

Aromatase, encoded by Cyp19a1, is the rate limiting enzyme in biosynthesis of estrogens, and excessive aromatase can reduce the semen quality in roosters. Seminal plasma extracellular vesicles (SPEV) are nanoscale vesicles that carry and transmit signaling molecules, thereby affecting semen quality. Currently it is still unclear whether SPEV are involved in the process of that aromatase affects the quality semen in chicken. To clarify this issue, lentivirus carrying Cyp19a1 (LV-CYP19A1) for over-expression of aromatase was constructed and injected to testis of 35-week-old roosters. Semen quality and seminal plasma hormone were measured, and SPEV were also extracted and proteome sequencing was performed after treatment of LV-CYP19A1. The results indicated that semen volume, fertility, sperm motility, testosterone (T) levels were significantly decreased, and estradiol (E Our results reveal that aromatase can down-regulate the protein expression related to regulation of ATP synthesis and metabolism, and sperm motility in SPEV, thereby reducing semen quality in roosters. Show less

Patients with diabetic nephropathy (DN) often present with lipid profile abnormalities. While associations between these parameters and DN have been suggested, confounding factors obscure causal relationships. This study employed bidirectional Mendelian randomization (MR) to explore these links. Using genome-wide association study (GWAS) data, the primary analysis used the inverse-variance weighted (IVW) method, which was supported by MR-Egger regression and a weighted median estimator (WME). Sensitivity analyses, including heterogeneity, pleiotropy tests, leave-one-out, and reverse causality analyses, were conducted. The IVW model revealed the following: (1) causal relationships between triglycerides (TG) (OR: 1.5807, 95% CI: 1.2578-1.9865, P = 0.0001), high-density lipoprotein cholesterol (HDL-C) (OR: 0.7342, 95% CI: 0.5729-0.9409, P = 0.0146), and apolipoprotein A1 (ApoA1) (OR: 0.6506, 95% CI: 0.5190-0.8156, P = 0.0002) and DN; (2) causal relationships between TG (OR: 1.0607, 95% CI: 1.0143-1.1093, P = 0.0098), HDL-C (OR: 0.9453, 95% CI: 0.9053-1.9871, P = 0.0109), and apolipoprotein B (ApoB) (OR: 1.0672, 95% CI: 0.0070-1.1310, P = 0.0280) and the urinary albumin-creatinine ratio (UACR); (3) no causal relationship between total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), ApoB and DN, or between TC, LDL-C, ApoA1 and UACR; (4) none of the results showed reverse causality. TG is a risk factor for DN and UACR; HDL-C is protective for both; ApoA1 protects against DN; and ApoB is a risk factor for UACR. To further explore the underlying mechanisms between TG, HDL-C, ApoA1, ApoB, and their associations with DN and UACR, and to provide reference for the selection of lipid management and treatment strategies for clinical DN patients. This study demonstrated that causal relationships between TG, HDL-C, and ApoA1 with DN and between TG, HDL-C, and ApoB with the UACR. Show less

The gut microbiota plays a crucial role in human health, but its impact on lipid metabolism remains unclear. Understanding the causal relationship between gut bacteria and lipid profiles is essential for developing strategies to prevent and treat dyslipidemia and cardiovascular diseases. This study aimed to assess this relationship using two-sample Mendelian randomization (MR). Data for both exposure and outcomes were obtained from the IEU-GWAS database, with lipid profile data sourced from a publication. Genome-wide significant single nucleotide polymorphisms (SNPs), which were independent of outcome factors but correlated with exposure variables, were identified as instrumental variables. Several MR methods, including weighted analysis, maximum likelihood, inverse variance weighting (IVW), MR-Egger, and weighted median, were applied. Colocalization analysis further validated the findings. The analysis revealed microbial groups with causal relationships to ApoA1, ApoB, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, total cholesterol, and triglycerides. Reverse MR and colocalization analysis provided additional confirmation of these results. This study offers new evidence of the causal link between gut microbiota and lipid profiles, providing insights for improving lipid profiles and reducing cardiovascular disease risk. Show less

To establish the reference interval for the serum lipid index in pregnant women and to explore the relationship between lipid metabolism levels and pregnancy outcomes. Data were derived from 446 pregnancy women and 317 healthy non-pregnant women. Serum levels of total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), apolipoprotein A1 (ApoA1), apolipoprotein B (ApoB), lipoprotein (a) [Lp(a)], and hypersensitive C-reactive protein (hs-CRP) were measured in both groups. The mean and standard deviation of each index were calculated to establish the reference range of normal serum lipid levels in pregnant women in mid-to-late pregnancy. The associations between serum lipid levels and perinatal outcomes were assessed statistically. There were no significant differences in age, pregnancy, or parity between the adverse outcome and normal delivery groups, but the caesarean section rate was significantly higher in the adverse outcome group. The levels of hs-CRP, TG, TC, HDL-C, LDL-C, and ApoA1 were significantly higher in the adverse outcome group. Elevated hs-CRP, TG, and HDL-C levels were risk factors for adverse pregnancy outcomes. According to the receiver operating characteristic curve, the optimal threshold of the combined diagnosis of these three indicators to predict adverse pregnancy outcomes was 0.534, and the area under the curve was 0.822. The establishment of lipid reference intervals in the second and third trimesters of pregnancy can effectively evaluate lipid metabolism in pregnant women, and the measurement of lipid metabolism in pregnant women is helpful in predicting adverse pregnancy outcomes. Show less

The causal relationship between the familial hypercholesterolemia (FH) and intestinal vascular diseases was unnoticed. This study aims to investigate the cause-and-effect relationship of FH with risk of intestinal vascular diseases in human. A Mendelian randomization (MR) analysis was performed by extracting summary-level datasets for FH or FH concurrently with ischemic heart disease (IHD) and intestinal vascular diseases from the FinnGen study including 329,115, 316,290 and 350,505 individuals. The inverse-variance weighted (IVW) method and the weighted median method were applied to analyze the causal relationships between FH or FH concurrently with IHD and the risk of intestinal vascular diseases. Cochran's Q statistic method and MR-Egger regression were used to assess heterogeneity and pleiotropy. The IVW method demonstrated that FH was significantly associated with higher odds of intestinal vascular diseases [OR (95%CI): 1.22 (1.03, 1.45)] ( In conclusion, FH was causally positive-associated with the increased risk of intestinal vascular diseases, revealing a potential unfortunate outcome for FH. Therefore, patients with FH should pay closely attention to the risk of intestinal vascular diseases. Our study may provide evidence for new diagnostic and therapeutic strategies in clinical practices. Show less

Eimeria tenella (E. tenella) infection is a major cause of coccidiosis in chickens, leading to significant economic losses in the poultry industry due to its impact on the cecum. This study presents a comprehensive single-cell atlas of the chicken cecal epithelium by generating 7,394 cells using 10X Genomics single-cell RNA sequencing (scRNA-seq). We identified 13 distinct cell types, including key immune and epithelial populations, and characterized their gene expression profiles and cell-cell communication networks. Integration of this single-cell data with bulk RNA-seq data from E. tenella-infected chickens revealed significant alterations in cell type composition and state, particularly a marked decrease in APOB Show less

Saturated fatty acid (SFA) and unsaturated fatty acid (UFA) have distinct impacts on health. Whether SFA and UFA are differentially transported in liver remains elusive. Here, we find the secretion of UFA but not SFA esters is retarded in a male mouse hepatic endoplasmic reticulum (ER) stress model. Among 13 members of protein disulfide isomerase (PDI) family, only PDIA1 (PDI) deficiency leads to hepatosteatosis and hypolipidemia. In PDI-deficient male mouse liver, there is a severe accumulation but secretory blockade of UFA esters, whereas the accumulation and secretion of SFA esters remain normal. PDI catalyzes the oxidative folding of microsomal triglyceride transfer protein (MTP). In addition, PDI deficiency in hepatocytes abolishes Apolipoprotein B-100 (ApoB-100) very low-density lipoprotein (VLDL) secretion while maintaining partial ApoB-48 VLDL secretion. In summary, we find that the secretion of UFA esters is PDI-MTP indispensable, while SFA esters could be transferred out of liver via ApoB-48 VLDL through a PDI-MTP-independent pathway. Show less

In preliminary research and literature review, we identified a potential link between chronic obstructive pulmonary disease (COPD) and lipid metabolism. Therefore, this study employed Mendelian randomization (MR) analysis to investigate the potential causal connection between blood lipids and COPD. A genome-wide association study (GWAS) on COPD was conducted, encompassing a total of 112,583 European participants from the MRC-IEU. Additionally, extensive UK Biobank data pertaining to blood lipid profiles within European cohorts included measurements for low-density lipoprotein cholesterol (LDL-C) with 440,546 individuals, high-density lipoprotein cholesterol (HDL-C) with 403,943 individuals, triglycerides (TG) with 441,016 individuals, total cholesterol (TC) with 187,365 individuals, apolipoprotein A-I (apoA-I) with 393,193 individuals, and apolipoprotein B (apoB) with 439,214 individuals. Then, MR analyses were performed for lipids and COPD, respectively. The primary analytical technique employed was the inverse-variance weighted (IVW) approach, which included a 95% confidence interval (CI) to calculate the odds ratio (OR). Additionally, a sensitivity analysis was conducted to assess the dependability of the MR analysis outcomes. MR analysis was primarily based on IVW, unveiled a causal link between COPD and LDL-C (OR=0.994, 95% CI (0.989, 0.999), P=0.019), TG (OR=1.005, 95% CI (1.002, 1.009), P=0.006), and apoA-I (OR=0.995, 95% CI (0.992, 0.999), P=0.008), in addition, no causal link was found with HDL-C, TC, apoB. Sensitivity analysis demonstrated the robustness of these causal relationships. However, through multivariate MR(MVMR) and multiple testing correction, LDL-C and TG had no causal effect on the outcome. ApoA-I remained a protective factor for the risk of COPD (OR=0.994, 95% CI (0.990-0.999), P=0.008). Through MR analysis, this study offers evidence of a causal link between apoA-I with COPD. This further substantiates the potential role of lipid metabolism in COPD, and has significant clinical implications for the prevention and management of COPD. Show less

At present, there is no consensus on the relationship between selenium (Se) exposure and human serum lipid metabolism. The etiological role of high-Se exposure in lipid markers, dyslipidemia, and nonalcoholic fatty liver (NAFLD) remains unclear. We used serum untargeted metabolomics analysis to evaluate whether high-Se exposure is cross-sectionally associated with lipid metabolism in adults from high-Se exposure area (n = 112) and control area (n = 101) in Hubei Province, China. An untargeted liquid chromatography/mass spectrometry (LC/MS)-based metabolomic analysis identified 144 differential pathways and yielded 204 differentially abundant metabolites, including 32 lipid metabolites associated with lipids profiles. To further explore the correlation between Se exposure and serum lipid metabolism, we measured serum levels of lipid profiles among all the people, including serum cholesterol (CHOL), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and apolipoprotein B (APOB). The average serum Se level of the high-Se exposure group was 537.18 μg/L, significantly higher than 72.98 μg/L in the control group (p < 0.0001). The measurement levels of serum TG, LDL-C, HDL-C, and APOB in the high-Se exposure group were 1.03 (0.76, 1.34) mmol/L, 2.25 ± 0.48 mmol/L, 1.12 ± 0.24 mmol/L, and 0.77 ± 0.15 g/L, respectively, while the control group were 1.13 (0.84, 1.80) mmol/L, 2.56 ± 0.61 mmol/L, 1.02 ± 0.22 mmol/L, and 0.83 ± 0.16 g/L, respectively (all p values <0.05). Correlation analysis showed a significant negative correlation between serum Se and CHOL (r = -0.201, p < 0.01), serum Se is also associated with metabolomics markers, the negative correlation includes glyceric acid and ect., the positive correlation includes phosphorylcholine and ect. Our study suggests that high-Se exposure is negatively associated with serum lipid profiles and decreases the risk of high-TC and HDL-C dyslipidemia. Show less

Elevated lipoprotein(a) (Lp[a]) and apolipoprotein B (apoB) are individually associated with the risk of atherosclerotic cardiovascular disease (ASCVD). Moreover, previous basic research has implicated the potential interaction between apoB and Lp(a) in the atherogenic process. We aimed to determine whether apoB levels significantly modulate ASCVD risk associated with Lp(a) in a large community-based population without baseline cardiovascular disease. Plasma Lp(a) and apoB were measured in the Atherosclerosis Risk in Communities (ARIC) study. Elevated Lp(a) was defined as the highest race-specific quintile, and elevated apoB was defined as ≥89 mg/dl (median value). The modifying effect of apoB on the Lp(a)-related risk of ASCVD and coronary heart disease (CHD) was determined using Cox regression models adjusted for cardiovascular risk factors. Among 12,988 ARIC participants, 3,888 ASCVD events and 1754 CHD events were observed. Elevated apoB (≥89 mg/dl) and elevated Lp(a) (race-specific quintile 5) were independently associated with ASCVD (hazard ratio [HR]: 1.19; 95% CI: 1.08-1.30; P <0.001; HR: 1.27; 95% CI: 1.16-1.40; P < .001, respectively). Lp(a)-by-apoB interaction was noted [Lp(a) (quintile 1-4 or quintile 5) * apoB (<89 or ≥89 mg/dl) = 0.002]. Compared to the concordantly low Lp(a) group, the individuals with high Lp(a) had a greater ASCVD risk only when apoB was elevated (HR: 1.48; 95% CI: 1.34-1.63; P < .001). In the context of primary prevention, ASCVD risk associated with Lp(a) was observed only when apoB was elevated. The measurement of apoB can further refine and contextualize the ASCVD risk associated with Lp(a). Show less

Liver cancer is the sixth most frequent malignancy and the fourth major cause of deaths worldwide. The current treatments are only effective in early stages of cancer. To overcome the therapeutic challenges and exploration of immunotherapeutic options, broad spectral therapeutic vaccines could have significant impact. Based on immunoinformatic and integrated machine learning tools, we predicted the potential therapeutic vaccine candidates of liver cancer. In this study, machine learning and MD simulation-based approach are effectively used to design T-cell epitopes that aid the immune system against liver cancer. Antigenicity, molecular weight, subcellular localization and expression site predictions were used to shortlist liver cancer associated proteins including AMBP, CFB, CDHR5, VTN, APOBR, AFP, SERPINA1 and APOE. We predicted CD8+ T-cell epitopes of these proteins containing LGEGATEAE, LLYIGKDRK, EDIGTEADV, QVDAAMAGR, HLEARKKSK, HLCIRHEMT, LKLSKAVHK, EQGRVRAAT and CD4+ T-cell epitopes of VLGEGATEA, WVTKQLNEI, VEEDTKVNS, FTRINCQGK, WGILGREEA, LQDGEKIMS, VKFNKPFVF, VRAATVGSL. We observed the substantial physicochemical properties of these epitopes with a significant binding affinity with MHC molecules. A polyvalent construct of these epitopes was designed using suitable linkers and adjuvant indicated significant binding energy (>-10.5 kcal/mol) with MHC class-I and II molecule. Based on in silico cloning, we found the considerable compatibility of this polyvalent construct with the E. coli expression system and the efficiency of its translation in host. The system-level and machine learning based cross validations showed the possible effect of these T-cell epitopes as potential vaccine candidates for the treatment of liver cancer. Show less

Patients with dyslipidemia are at higher risk for inflammatory bowel disease (IBD), yet the impact of lipid-lowering medications on IBD remains unclear. This study investigates the causal relationship between lipid-lowering drug target and IBD, with a focus on the roles of gut microbiota and inflammatory cytokines. Genetic variants associated with lipid-lowering drug targets were extracted from the Global Lipids Genetics Consortium, whereas summary statistics for IBD, Crohn's disease (CD), and ulcerative colitis were sourced from the International Inflammatory Bowel Disease Genetics Consortium. Drug-target Mendelian randomization analysis revealed that inhibiting angiopoietin-like protein 3 increased the risk of IBD and CD, whereas inhibition of apolipoprotein C-III (APOC3) heightened the risk of CD. Conversely, enhancement of LPL and LDL receptor reduced the risk of IBD and CD. Mediation analysis demonstrated that gut microbiota and inflammatory cytokines partially mediated these effects, with specific pathways such as Lachnospiraceae FCS020 (17.26%) for APOC3 and Clostridium sensu stricto 1 (20.12%) for LPL accounting for significant portions of the effects. These findings suggest that lipid-lowering drugs targeting angiopoietin-like protein 3 and APOC3 may increase the risk of IBD, whereas those targeting LPL and LDL receptor may reduce the risk. The results highlight potential for repurposing lipid-lowering drugs for IBD prevention and warrant future clinical trials to explore these targets further. Show less

Traumatic brain injury (TBI) is more common than ever and is becoming a global public health issue. A variety of secondary brain injuries occur after TBI, including ferroptosis characterized by iron-dependent lipid peroxidation. Gallic acid is a kind of traditional Chinese medicine, which has many biological effects such as anti-inflammatory and antioxidant. We further investigated whether Gallic acid can improve the neurological impairment caused by ferroptosis after TBI by targeting APOC3. Weighted gene coexpression network analyses (WGCNA) and 3 kinds of machine-learning algorithms were used to find the potential biomarkers. Then the HERB database was used to select the Chinese herb that acted on the target gene APOC3. Finally, we selected Gallic acid as a drug targeting APOC3 and verified by Western blotting. The effect of Gallic acid on the improvement of neurological function was studied by Nissl staining and FJB staining. Finally, the effect of Gallic acid on the cognitive ability of TBI mice was explored through behavioral experiments. Gallic acid can inhibit the expression level of APOC3 and thus inhibit the level of ferroptosis after TBI. It can also reduce the degeneration of nerve tissue by inhibiting ferroptosis and improve the neurological function deficit. The behavioral experiment proved that Gallic acid can alleviate the behavioral cognitive impairment caused by TBI. Gallic acid can reduce ferroptosis by inhibiting APOC3, and then alleviate neurological impairment after TBI. Show less

Idiopathic pulmonary fibrosis (IPF) is a fatal interstitial lung disease with limited therapeutic options, thus necessitating novel strategies targeting upstream fibrogenic drivers; the exact impact of apolipoprotein E (apoE) on IPF and its therapeutic potential remain unexplored. This study aims to identify novel therapeutic targets for pulmonary fibrosis and elucidate the mechanism by which plasma apoE alleviates this condition. We conducted an integrated meta-analysis of seven plasma cohorts and two-sample Mendelian randomization to assess apoE's association with IPF risk. CRISPR-engineered APOE-deficient canines and Apoe Plasma apoE was identified as a robust protective factor against IPF, with genetically elevated levels correlating with improved pulmonary function, and its deficiency in plasma showed potential diagnostic value for IPF. APOE-deficient canines developed spontaneous pulmonary fibrosis, and Apoe Plasma apoE is a causal guardian against pulmonary fibrogenesis, inhibiting TGF-β/Smad signaling through dual receptor (LRP1/PLAU) engagement. Cross-species validation and mechanistic elucidation position RGX-104, a small-molecule LXR agonist, as a potential therapeutic candidate for clinical translation in IPF. Show less

Atherosclerotic cardiovascular disease (ASCVD) is a leading cause of death. Systemic autoimmune and inflammatory diseases are associated with increased ASCVD risk, severity, and mortality. The inflammatory cytokine interleukin 9 (IL-9) has been linked to murine atherogenesis, raising fundamental questions about the populations in which and the mechanisms by which IL-9 drives ASCVD. Circulating T helper subsets and coronary computed tomography angiography data were analysed in patients with psoriasis. Murine models of psoriatic atherogenesis (imiquimod-ApoE Here, we found that expansion of IL-9-producing T helper cells (Th9) was significantly associated with high-risk radiographic ASCVD in patients with the autoimmune disease psoriasis. Th9 cells were poised to migrate to coronary vessels and were identified in human atherosclerotic plaque from individuals with psoriasis. In vivo, murine inflammatory atherogenesis was prevented by IL-9 blockade and by IL-9 receptor (IL-9R) deletion in endothelial cells. In human arterial endothelial cells, IL-9R/STAT3 signalling promoted endothelial dysfunction via diverse mechanisms including adhesion, activation, angiogenesis, and release of leukocyte chemoattractants. These findings suggest the Th9 Show less

Regular exercise training has been shown to significantly decrease atherosclerosis (AS) related mortality and hospitalization rates. Recent research has identified that circulating exosome-derived microRNAs (miRNAs) are closely related to the progression of AS through intercellular communication. But the role of exosome-derived miRNAs in exercise-mediated protection remains to be explored. This study proposes that exercise may ameliorate vascular dysfunction and plaque formation associated with AS by modulating the expression profile of exosomal miRNAs. In this study, ApoE Show less

Acupuncture has been proposed as a therapeutic intervention for stroke recovery, yet the underlying molecular mechanisms remain poorly understood. In this study, we used a mouse model of hemorrhagic stroke induced by autologous blood injection to investigate the effects of acupuncture on post-stroke recovery at the cellular and molecular levels, utilizing single-cell RNA sequencing. Our findings revealed that acupuncture modulates the gene expression of microglia, astrocytes, and oligodendrocytes, three major glial cell types, which may contribute to the improvement of stroke-induced phenotypes. Notably, we identified a potential role of the APOE-TREM2 signaling axis, with ligand-binding interactions enhancing microglia activation and promoting their neuroprotective functions. These findings also suggested that acupuncture may promote microglia-astrocyte interactions, leading to enhanced neuroinflammation resolution and tissue repair. Our study provided new insights into the cellular mechanisms underlying acupuncture's therapeutic effects in stroke recovery and highlighted the potential of targeting glial cell-mediated pathways, including APOE-TREM2, as a strategy for improving post-stroke rehabilitation. Show less

Rupture of vulnerable atherosclerotic plaques is a major cause of acute cardiovascular events. Vascular smooth muscle cell (VSMC) senescence promotes plaque vulnerability by impairing fibrous cap integrity. Although melatonin exhibits atheroprotective potential, its capacity to stabilize plaques by targeting VSMC senescence along with the underlying mechanisms, remains unclear. In this study, a vulnerable plaque model was established in ApoE Show less

Aortic dissection (AD) involves complex interactions among amino acid, glucose, and lipid metabolism, exacerbating aortic inflammation and extracellular matrix (ECM) degradation, coupled with smooth muscle cell (SMC) dysfunction (phenotypic alteration, aging, apoptosis). To explore AD pathogenesis, we integrated single-cell RNA sequencing (scRNA-seq), metabolomics, machine learning, and Mendelian randomization to investigate SMC changes and gene-metabolite interactions. ScRNA-seq data (GSE213740, GSE155468) were analyzed for cell clustering and pseudo-time trajectories via Seurat and Monocle2. Metabolomics (9 samples: 6 AD, 3 controls) and machine learning validated key genes/metabolites, with Mendelian randomization assessing causal links. Nine cell subsets and 2000 variable genes were identified, with SMCs central to AD via cholesterol metabolism. APOE and PLTP were key genes; metabolomics highlighted cholesterol esters (CEs) and triglycerides (TGs) as critical metabolites. Machine learning confirmed APOE/PLTP's high predictive accuracy (AUC: 0.796-0.989). Mendelian randomization linked elevated CEs and TGs to increased AD risk (IVW: P = .04 and P = .02, respectively). This study establishes a gene-metabolite network where APOE and PLTP regulate CEs/TGs, influencing SMC function and AD progression, offering potential therapeutic targets. Show less

Histone deacetylase 3 (HDAC3) is an epigenetic modifying enzyme closely linked to the development of atherosclerosis. Endothelial inflammation is a critical factor in atherosclerosis. However, the role of HDAC3 in mediating epigenetic modifications and regulating endothelial inflammation in atherosclerosis remains unclear. This study aims to investigate the impact of HDAC3 on endothelial inflammation and its contribution to atherosclerosis. Firstly, single-cell transcriptomic analysis identified elevated expression of HDAC3 and nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) in inflammatory endothelial cells of atherosclerotic plaques in symptomatic patients. Endothelial-specific knockout HDAC3 in an apolipoprotein E knockout (ApoE Show less

Cyclophosphamide (CTX), a cornerstone in breast cancer combination chemotherapy, frequently induces adverse effects including myelosuppression, gastrointestinal disturbances, hepatic impairment, and alopecia. Chemotherapy-induced alopecia severely impacts patients' quality of life and psychological well-being. Modified Huanjingjian (MHJJ), a traditional Chinese herbal formula, demonstrates clinical efficacy in alleviating chemotherapy-related side effects, yet its mechanisms against CTX-induced alopecia remain uncharacterized. And our main aim was to explore the efficacy and the mechanism of MHJJ in mice. UPLC-QE-Orbitrap-MS characterized MHJJ's chemical composition. A CTX-induced alopecia murine model was established. Systemic toxicity was evaluated through body weight monitoring, automated biochemical analysis (ALT/AST levels), and hematological profiling (WBC/PLT counts). Hair follicle histopathology was assessed via H&E staining. IHC and IF staining quantified proliferation markers and hair follicle stem cell (HFSC) biomarkers. Reduced representation bisulfite sequencing (RRBS) was used to map DNA methylation patterns. Wnt pathway dynamics were analyzed through qRT-PCR and IF staining. We identified 110 bioactive compounds in MHJJ. MHJJ intervention attenuated alopecia severity, restored follicular architecture, and increased follicular density compared to CTX monotherapy (p<0.05). HFSC proliferation markers (Ki67/CD34) showed significant upregulation, while apoptosis markers (Caspase-3) were suppressed. RRBS revealed MHJJ-mediated hypomethylation in differentially methylated regions, with gene body methylation constituting 60% of total methylation changes. Methylation-modulated genes predominantly localized to Wnt signaling pathways: MHJJ enhanced Wnt3/Wnt10a expression while suppressing Cer1/Axin1. Corresponding methylation reductions at promoter and gene body regions were confirmed at mRNA and protein levels. MHJJ mitigates CTX-induced alopecia through epigenetic regulation of HFSCs, specifically via DNA hypomethylation-mediated activation of Wnt3/Wnt10a and suppression of Cer1/Axin1. This mechanism promotes follicular regeneration by restoring Wnt signaling homeostasis, positioning MHJJ as a promising adjuvant for chemotherapy-induced alopecia management. Show less

Patients with Alzheimer's disease (AD) demonstrate brain mitochondrial dysfunction and energy deficiency that are closely associated with cognitive impairment. Cytochrome c oxidase (CCO), also known as mitochondrial complex IV, is the terminal enzyme in mitochondrial electron transport chain (ETC). Consistent with the pivotal role of CCO in mitochondrial bioenergetics and high demand for energy to sustain neuronal function, CCO dysfunction has been linked to neurological disorders including AD. However, it remains unclear whether mitochondrial CCO dysfunction represents an adaptive response to AD-associated toxic molecules versus a Show less

Alzheimer's disease (AD) is a progressive neurodegenerative disorder and the leading cause of dementia, with current therapies offering only limited symptomatic relief and lacking disease-modifying efficacy. Addressing this critical therapeutic gap, natural multi-target compounds like mulberroside A (MsA)-a bioactive glycoside from Show less

BackgroundAlzheimer's disease (AD) is a neurodegenerative disorder characterized by pathogenesis involving numerous factors. Recent research has highlighted the significant role of autoimmunity in the initiation and progression of AD, with autoantibodies emerging as a pivotal area of investigation. Nevertheless, the influence of autoantibodies in AD is marked by substantial heterogeneity, they may either mitigate disease progression by clearing pathogenic protein aggregates or exacerbate the pathological process through mechanisms such as the activation of inflammatory responses or the induction of neuronal damage.ObjectiveThis review aims to synthesize the various roles of autoantibodies in AD, examine the factors that influence their functions, and assess their potential application in precision immunotherapy.MethodsPubMed and Web of Science databases were searched for English-language papers (2015-2025). Peer-reviewed human, animal and cell studies, systematic reviews and meta-analyses were screened independently by two reviewers.ResultsA total of 87 studies were selected for inclusion, spanning human, animal, and cellular research. The findings indicated that certain autoantibodies, such as those targeting amyloid-β, tau, or 4-hydroxynonenal, may confer neuroprotective effects. Conversely, other autoantibodies, including those against BACE1, aquaporin-4, or HuD, may exacerbate AD pathology. Importantly, some autoantibodies were found to exhibit dual roles, contingent upon their specific modifications or the context of the disease.ConclusionsAutoantibodies constitute a double-edged immune axis in AD. Their impact hinges on antigen class, disease stage, isotype affinity and glycosylation. Precision strategies-like CAAR-T cell therapy, glycosylation modulation, and affinity optimization-offer therapeutic promise but require further validation. Show less